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Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis.

Das Sarma J, Ciric B, Marek R, Sadhukhan S, Caruso ML, Shafagh J, Fitzgerald DC, Shindler KS, Rostami A - J Neuroinflammation (2009)

Bottom Line: IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion.Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. dassarmaj@iiserkol.ac.in

ABSTRACT

Background: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

Methods: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA.

Results: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.

Conclusion: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions.

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Exogenous treatment of IL-17A does not alter IL-17RA expression in glial culture. mRNA was isolated from either non-treated resting culture or IL-17A (10 ng/ml) treated culture supernatants at 12 hr in vitro. IL-17RA gene expression was measured by RT-PCR using a primer set from exon boundary 1–2. Data represent the mean expression from three different non- treated and IL-17A- treated culture batches ± SEM. IL-17A treatment did not alter IL-17RA expression in neonatal glial cells (*p > 0.05).
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Figure 8: Exogenous treatment of IL-17A does not alter IL-17RA expression in glial culture. mRNA was isolated from either non-treated resting culture or IL-17A (10 ng/ml) treated culture supernatants at 12 hr in vitro. IL-17RA gene expression was measured by RT-PCR using a primer set from exon boundary 1–2. Data represent the mean expression from three different non- treated and IL-17A- treated culture batches ± SEM. IL-17A treatment did not alter IL-17RA expression in neonatal glial cells (*p > 0.05).

Mentions: To ensure that changes in chemokine expression induced by IL-17A were due to signaling through constitutively expressed IL-17RA, as opposed to an increase of IL-17RA expression, we evaluated the influence of IL-17A treatment on IL-17RA expression in astrocytes and microglia. IL-17A did not significantly alter the constitutive expression of IL-17RA mRNA (p > 0.05) (Figure 8). This infers that upregulation of chemokines by glial cells was due to exogenous IL-17A signaling through constitutively expressed IL-17RA.


Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis.

Das Sarma J, Ciric B, Marek R, Sadhukhan S, Caruso ML, Shafagh J, Fitzgerald DC, Shindler KS, Rostami A - J Neuroinflammation (2009)

Exogenous treatment of IL-17A does not alter IL-17RA expression in glial culture. mRNA was isolated from either non-treated resting culture or IL-17A (10 ng/ml) treated culture supernatants at 12 hr in vitro. IL-17RA gene expression was measured by RT-PCR using a primer set from exon boundary 1–2. Data represent the mean expression from three different non- treated and IL-17A- treated culture batches ± SEM. IL-17A treatment did not alter IL-17RA expression in neonatal glial cells (*p > 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2689857&req=5

Figure 8: Exogenous treatment of IL-17A does not alter IL-17RA expression in glial culture. mRNA was isolated from either non-treated resting culture or IL-17A (10 ng/ml) treated culture supernatants at 12 hr in vitro. IL-17RA gene expression was measured by RT-PCR using a primer set from exon boundary 1–2. Data represent the mean expression from three different non- treated and IL-17A- treated culture batches ± SEM. IL-17A treatment did not alter IL-17RA expression in neonatal glial cells (*p > 0.05).
Mentions: To ensure that changes in chemokine expression induced by IL-17A were due to signaling through constitutively expressed IL-17RA, as opposed to an increase of IL-17RA expression, we evaluated the influence of IL-17A treatment on IL-17RA expression in astrocytes and microglia. IL-17A did not significantly alter the constitutive expression of IL-17RA mRNA (p > 0.05) (Figure 8). This infers that upregulation of chemokines by glial cells was due to exogenous IL-17A signaling through constitutively expressed IL-17RA.

Bottom Line: IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion.Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. dassarmaj@iiserkol.ac.in

ABSTRACT

Background: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

Methods: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA.

Results: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.

Conclusion: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions.

Show MeSH
Related in: MedlinePlus